The main character in the book, of course, is the famous detective Sherlock Holmes. Holmes is a brilliant thinker and delights in the excitement of "the chase". In addition, he is rather an eccentric character who takes only those cases which interest him, has a penchant for dramatic flair, and is capable of forming amazing deductions from seemingly insignificant clues.

Dr. John Watson is Holmes's friend and assistant. He provides a good balance for the detective's quirky personality, being himself intelligent, energetic, courageous, and loyal. It is Watson who narrates the story, as he does almost all of Sherlock Holmes's adventures.

Sir Henry Baskerville, the last known heir in the Baskerville line, has a fiery temper and a mind of his own. Although he is an impeccable gentleman, he is independent and tends to follow his own inclinations, sometimes making it difficult for Holmes to both ensure his safely and solve the case.

Dr. James Mortimer is a young country physician and a friend of Sir Henry. It is he who first appeals to Sherlock Holmes for help in keeping the heir of the Baskerville family safe.

The villain in the story is Stapleton, a respected naturalist and a reknowned authority in entymology. Despite his innocuous appearance he has a keen mind, and has devised an ingenious way to use the legend of the Hound of the Baskervilles to his advantage.